The overall goal of this project is to understand control of normal cell flow distribution in the microcirculation. we are interested in understanding, at a quantitative level, how cell flow distribution at individual bifurcations is modified by local bifurcation geometry, how cell rheological properties (deformability) influence flow distribution, and how architecture and hemodynamic properties (flow, cell concentration) are related to the overall distribution of cells in connected microvascular networks. We take the view that the apparent heterogeneity of cell distribution observed in intact systems is not random variability but reflects an expected outcome of locally predictable architectural, hemodynamic and rheological features. The main focus of the project is thus on understanding determinants of cell distribution at bifurcations at defined locations in small arterioles and capillaries, and on developing a quantitative overview of how these elements influence their neighbors in a connected system. We will work closely with Dr. Waugh and Dr. Knauf (Project 2) in our investigations of how cell deformability influences cell distribution into capillaries. In the early part of the study, our role will be mainly to define in vivo survival times of variously modified cells produced by Project 2; subsequently we will obtain cells with defined properties from Project 2 and will study their flow properties in capillaries. We expect to interact closely with Dr. Cokelet (Project 5) in many aspects of our investigations of phase separation at defined arteriolar bifurcations and across capillary networks, particularly in the local and network architectural studies of Aims l and 2; our approach to quantitation of HD ratios at bifurcations was developed with Dr. Cokelet, and we expect to continue a significant shared interest in many of the studies proposed in both projects.